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Biomedical subjects

M V Pimm

Publications and source records attributed to M V Pimm.

At least 127 records · Page 7Linked to original sources
PubMed1979

Serological aspects of rat tumour xenograft growth in athymic nude mice.

The serum of athymic nude mice bearing rat tumour xenografts has been examined for tumour-specific antigen. With a sarcoma and a hepatoma, tumour-specific antigen expression continued in xenograft growths, and sera of tumour-bearing mice contained free antigen, assayed by its ability to neutralise reactivity of tumour-immune rat sera against tumour target cells in an indirect membrane-immunofluorescence test. In contrast, no anti-rat antibody was detectable in sera of mice bearing the xenografts, or rejecting cells injected in admixture with BCG.

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PubMed1979

Quantitative comparison of BCG strains and preparations in immunotherapy of a rat sarcoma.

Ten preparations of BCG, six clinical vaccines, and four experimental preparations were compared for suppression of tumor growth by regional application. The preparations differed widely in their proportions of viable bacterial units and in bacterial unit:dry weight ratios. As assessed by their ability to suppress tumor development following direct admixtures with cell inocula of a rat sarcoma, one of the six clinical vaccines (Connaught) was significantly superior to Glaxo on any parameter (dry weight, No. of total units, or No. of viable units), immuno BCG Pasteur F was superior to Glaxo on two parameters (dry weight and No. of viable units), and Pasteur scarification was superior to Glaxo only on a viable unit basis. The Tice and Rijks Institute vaccines were not significantly different from Glaxo on any basis. Experimental vaccines from the Trudeau Mycobacterial Collection, stored as frozen liquid suspensions, showed a less marked variation in physical properties; here too, the Pasteur strain was superior to two other Trudeau preparations examined (Tice and Phipps). Viable organisms were not essential for tumor suppression, gamma-radiation-sterilized vaccine being equally effective. Tests with pulmonary tumor deposits, treated by iv BCG, and tests with pleural deposits, treated by intrapleural BCG, indicated that agents identified as superior in the subcutaneous screening system were also superior in the treatment of thoracic deposits.

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PubMed1978

BCG treatment of transplanted rat tumours of spontaneous origin.

Six transplanted rat tumours (three mammary carcinomas and three fibrosarcomas), all of spontaneous origin and of limited immunogenicity, have been examined for susceptibility to immunotherapy with BCG (Glaxo). Growth of limited numbers of cells from five tumours was suppressed when cells were injected subcutaneously in admixture with BCG organisms. There was no clear correlation between the immunogenicity of tumour lines and their susceptibility to regionally applied BCG. Active specific immunotherapy, using vaccines of viable or radiation-attenuated tumour cells in admixture with BCG, was reproducibly successful with only one tumour, the mammary carcinoma Sp4, this being the most immunogenic of the tumours examined. These studies indicate that naturally arising tumours are less susceptible to BCG-mediated suppression than carcinogen-induced tumours widely used for experimental immunotherapy, but indicate that local application of BCG may give the best therapeutic response.

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PubMed1978

BCG treatment of human tumour xenografts in athymic nude mice.

Xenografts of 3 human malignant cell lines in congenitally athymic nude mice have been examined for susceptibility to BCG. Growth of all 3 tumours, a bladder carcinoma, a melanoma and a colon carcinoma, was suppressed when cells were injected in admixture with BCG. Distant injection of BCG was ineffective. Mice with progressive growths had no detectable anti-human antibody, and rejection of cells and BCG failed to confer protection against subsequent tumour challenge. These studies indicate that human malignant cells are susceptible to local BCG-activated host responses, and that athymic mouse xenografts may be a useful model for assessing the response of human tumours to such agents.

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PubMed1977

C. parvum immuntherapy of transplanted rat tumours.

C.parvum (Wellcome CN 6134) has been tested for tumour suppression against a range of syngeneically transplanted rat tumours, both carcinogen-induced and of spontaneous origin. Subcutaneous growth was not prevented by distant subcutaneous or intravenous injection of the preparation, although growth rates were sometimes depressed or accelerated. In contrast, C. parvum injected in admixture with tumour cells consistently suppressed their growth and with highly immunogenic tumours induced systemic tumour immunity, C. parvum injected intravenously retarded development of pulmonary tumour deposits, and intrapleural injection suppressed growth of pleural tumours and malignant effusions. Host immunosuppression failed to abrogate the tumour-suppressive effect of locally applied C. parvum, but host macrophage depletion with silica totally abolished the response. These studies indicate that in the rat, tumour suppression is most consistently achieved by regional application of C. parvum, and that this response is more dependent upon local macrophage stimulation than generation of systemic immune responses.

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PubMed1977

Antigenic differences between primary methylcholanthrene-induced rat sarcomas and post-surgical recurrences.

The immunogenicities of in vivo lines established from primary MCA-induced rat sarcomas have been compared with those of lines initiated from tumour recurrences at the site of the primaries' surgical excisions. Lines from two of four primary sarcomas showed little or no immunogenicity, as assessed by protection against challenge afforded by graft excision or implantation of irradiated tissue. In contrast, lines from all four recurrences were immunogenic, giving protection against up to 5 X 10(6) tumour cells. Most importantly, with all four tumours, lines established from recurrences were antigenically distinct from lines derived from their original primary sarcomas, so that immunization with regrowth lines gave no protection against the lines from the primaries, and vice versa. These studies demonstrate that primary MCA-induced sarcomas are antigenically distinct from recurrent tumors arising after surgical removal of the primaries, implying that these tumours arose by clonal amplification of separate populations of transformed cells. This may reflect proliferation of dormant neoplastic cells or the further induction of transformed cells by residual carcinogen. These findings are relevant to the multifocal origin of tumours and for the design of active immunotherapy for the treatment of recurrences or metastatic deposits.

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PubMed1976

BCG treatment of malignant pleural effusions in the rat.

Intrapleurally injected cells of an ascitic rat tumour produced intrapleural effusions and solid pleural deposits. BCG, or its methanol extraction residue (MER) injected into the pleural space, suppressed tumour development and prolonged survival. Treatment was effective if given a few days before or after tumour injection. In contrast, active specific immunotherapy by repeated s.c. injection of viable or radiation-attenuated tumour cells in admixture with BCG was unsuccessful, and did not improve the response to intrapleural BCG treatment.

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PubMed1976

Treatment of transplanted rat tumours with double-stranded RNA (BRL 5907). I. Influenced of systemic and local administration.

Growth of transplanted rat tumours was retarded and in some cases completely suppressed when cells were injected subcutaneously in admixture with double stranded RNA (ds-RNA). This response required intimate contact between ds-RNA and tumour cells and systemic treatment with the agent failed to prevent progressive growth of a range of rat tumours. Direct cytotoxic effects of ds-RNA may contribute to tumour suppression since the compound was cytotoxic in vitro for cultured tumour cells. The involvement of host factors is suggested, however, by the in vivo tests showing variations in susceptibility to ds-RNA mediated tumour suppression similar to that previously observed with bacterial adjuvants.

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PubMed1976

Treatment of transplanted rat tumours with double-stranded RNA(BRL 5907). II. Treatment of pleural and peritoneal growths.

Intrapleural growth of transplanted rat tumours was prevented or retarded by intrapleural administration of double-stranded RNA. A similar suppression of growth was achieved with peitoneal tumours by the intraperitoneal injection of the compound. These studies indicate the possible potential of this form of treatment of thoracic and peritoneal tumours for clinical application in the treatment of mesothelioma.

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PubMed1976

Bacillus Calmette-Guérin contact immunotherapy of local and metastatic deposits of rat tumors.

Adjuvant contact therapy with BCG can be used to control tumor deposits at local subcutaneous sites and at other sites, particularly pulmonary metastases and pleural tumor growths. This treatment method is generally quantitatively more effective than general immunostimulation, or active immunotherapy that employs vaccines of adjuvant and tumor cells. Furthermore, this treatment is effective in hosts that lack full immunocompetence, making it still feasible in immunosuppressed patients. The current evidence indicates that local activation of host macrophages is probably the essential effector mechanism of adjuvant contact therapy.

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